US7314639B2 - Process for the production of crystals of a benzoic acid derivative - Google Patents
Process for the production of crystals of a benzoic acid derivative Download PDFInfo
- Publication number
- US7314639B2 US7314639B2 US10/344,690 US34469003A US7314639B2 US 7314639 B2 US7314639 B2 US 7314639B2 US 34469003 A US34469003 A US 34469003A US 7314639 B2 US7314639 B2 US 7314639B2
- Authority
- US
- United States
- Prior art keywords
- crystal
- benzoic acid
- carbamoyl
- tetrahydro
- tetramethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 133
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000004519 manufacturing process Methods 0.000 title description 3
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 title 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims abstract description 45
- MUTNCGKQJGXKEM-UHFFFAOYSA-N tamibarotene Chemical compound C=1C=C2C(C)(C)CCC(C)(C)C2=CC=1NC(=O)C1=CC=C(C(O)=O)C=C1 MUTNCGKQJGXKEM-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000000113 differential scanning calorimetry Methods 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 15
- 239000013557 residual solvent Substances 0.000 claims abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 238000001953 recrystallisation Methods 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims 4
- 238000002360 preparation method Methods 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract description 6
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000155 melt Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000000634 powder X-ray diffraction Methods 0.000 description 10
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 229940127557 pharmaceutical product Drugs 0.000 description 5
- 238000001914 filtration Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 208000011797 pustulosis palmaris et plantaris Diseases 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 238000001507 sample dispersion Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Definitions
- the present invention relates to a method for selective preparation of a particular crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid useful as an active ingredient of a medicament.
- this compound is known to exist at least as two kinds of crystal polymorphs, that is, (1) a crystal melting at 193° C. and (2) a crystal melting at 233° C. [see, Japanese Patent No. 3001632 as for (1), and Japanese Patent Unexamined Publication (Kokai) No. 61-76440 as for (2). (3) A crystal melting at 205.5° C. to 206.5° C. is disclosed in Chem. Pharm. Bull., 32, p.4209, 1984. However, this crystal was later reported to actually have the melting point of 231° C. to 232° C. and thus revealed to be identical to the crystal (2) (J. Cellular Physiology, 135, pp.179-188, 1988)].
- the crystal described in Japanese Patent No. 3001632, which melts at 193° C. is prepared by using a mixture of methanol and water as a recrystallization solvent.
- the crystal that melts at 233° C. is prepared by using a mixture of ethyl acetate and hexane as a recrystallization solvent.
- the latter crystal (melting point: 233° C.) contains 1200 ppm and 190 ppm of residual ethyl acetate and hexane, respectively, and thus has a problem that the crystal can hardly satisfy the standard values of residual solvents provided by the Ministry of Health and Welfare (ethyl acetate: 5000 ppm or less; hexane: 290 ppm).
- the crystal that melts at 193° C. has a characteristic feature that a residual methanol level can be significantly lowered.
- the crystal that melts at 193° C. has a problem that the crystalline form readily occurs transition by physical impact, and thus preparation thereof as a uniform crystal is extremely difficult. Accordingly, this crystal lacks an aptitude as a raw material for large scale manufacture of a pharmaceutical product that constantly meets quality standard. Whilst the crystal that melts at 233° C. has been revealed to have high stability against physical impact, as well as against heat, temperature, light and the like. However, a method for selective preparation of this crystal has not been known so far. Further, a method is known for preparation of the crystal that melts at 233° C. in which a mixture of ethyl acetate and hexane are used as a recrystallization solvent. However, hexane is classified as Class 2 solvent according to the guidelines for residual solvents of pharmaceutical products, and is undesirable solvent to be remained in pharmaceutical preparations. Accordingly, a crystal is strongly desired that does not contain hexane as a residual solvent.
- An object of the present invention is to provide a method for selective preparation of the crystal that melts at 233° C. among crystals of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid, and the above crystal that does not contain hexane as residual solvent.
- the inventors of the present invention conducted various studies to achieve the foregoing object. As a result, they found that the crystal that melts at 233° C. can be selectively prepared by recrystallization using a mixture of ethanol and water. Conventionally, it has been known that the crystal that melts at 193° C. can be selectively prepared by using a mixture of ethanol and water. It is indeed surprising that the crystal of different crystalline form can be selectively obtained by using the mixture of ethanol and water.
- the present invention thus provides a method for preparing a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid having a single endothermic peak approximately at 233° C. in differential scanning calorimetry, which comprises the step of recrystallizing a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid from a mixture of water and ethanol.
- the aforementioned method wherein a volume ratio of ethanol and water is in the range of 8:5 to 1:1 is provided.
- the present invention also provides a method for preparing a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid having a single endothermic peak approximately at 233° C. in differential scanning calorimetry, which comprises the step of heating a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid having endothermic peaks approximately at 193° C. and 233° C. in differential scanning calorimetry.
- the crystal can be heated at a temperature around 200° C.
- the present invention further provides a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid having a single endothermic peak approximately at 233° C.
- the present invention provides use of a crystal of the 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid having a single endothermic peak approximately at 233° C. in differential scanning calorimetry, which is characterized not to contain hexane and/or ethyl acetate as a residual solvent, for manufacture of a pharmaceutical product, and a medicament comprising the aforementioned crystal as an active ingredient.
- the aforementioned medicament include a medicament for therapeutic treatment of acute promyelocytic leukemia, a medicament for therapeutic treatment of psoriasis and pustulosis palmaris et plantaris and the like.
- Types of crystals of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid used as a raw material for the method of the present invention are not particularly limited. Any crystals may be used in addition to the crystal that melts at 193° C. (the aforementioned crystal (1)). According to the studies of the inventors of the present invention, the crystal that melts at 193° C. (referred to as “type-I crystal”) described in Japanese Patent No. 3001632 gives a single endothermic peak approximately at 194° C. in differential scanning calorimetry (DSC). Further, the crystal that melts at 233° C.
- DSC differential scanning calorimetry
- type-I crystal described in Japanese Patent Unexamined Publication No. 61-76440 gives a single endothermic peak approximately at 233° C. in differential scanning calorimetry.
- the inventors of the present invention has recognized the existence of a crystal that gives an endothermic peak approximately at 193° C. in differential scanning calorimetry and simultaneously occurs exothermic transition to give an endothermic peak approximately at 233° C. (referred to as “type-III crystal”, see, Example 3 of the specification).
- this crystal is defined as a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-aphthalenyl)carbamoyl]benzoic acid that has endothermic peaks approximately at 193° C. and 233° C. in differential scanning calorimetry. Any of the aforementioned crystals may be used as a raw material for the method of the present invention.
- Crystalline forms can be reliably identified by performing powder X-ray diffraction analysis in addition to differential scanning calorimetry.
- Powder X-ray diffraction patterns of the aforementioned type-I and type-II crystals are shown in FIGS. 5 and 6 of Japanese Patent No. 3001632 and can be easily identified by those skilled in the art. Further, the results of thermal analyses of the aforementioned type-I and type-II crystals are shown in FIGS. 3 and 4 of the aforementioned patent document, respectively.
- An experimental error in measurement of melting point, differential scanning calorimetry and the like is approximately a few degrees, usually within 2° C., preferably within 1° C., more preferably within 0.5° C.
- the method of the present invention is characterized in that a mixture of ethanol and water is used as a recrystallization solvent for 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid.
- a mixing ratio of ethanol and water at crystallization is not particularly limited.
- ethanol:water is preferably in the range of about 8:5 to 1:1. When the proportion of ethanol become higher than the above range, a mixture of type-I crystals and type-II crystals may sometimes be obtained.
- a process for recrystallization is not particularly limited, and an ordinary recrystallization process may be employed.
- a crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid as a raw material may be completely dissolved in a mixture of ethanol and water, and then the solution may be gradually cooled and precipitated crystals are collected by filtration.
- a crystal as a raw material may be dissolved in ethanol with heating, and then the solution may be added with an appropriate amount of hot water to prepare an ethanol-water mixture in a given ratio for crystallization of the desired substance.
- a seed crystal may be added.
- An amount of the seed crystal is not particularly limited.
- the amount may be about 1/1,000 to 1/1,000,000, preferably about 1/80,000, based on the weight of the crystal used as a raw material.
- the crystals collected by filtration can be generally dried with heating at about 110° C. to 120° C. under reduced pressure to remove the recrystallization solvent.
- a heating temperature may generally be 180° C. or higher, preferably 200° C. or higher, most preferably about 200° C. to 210° C.
- the crystal of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid provided by the method of the present invention is manufactured without using a recrystallization solvent containing hexane, and accordingly, the crystal is characterized not to substantially contain hexane as a residual solvent.
- residual ethanol contained in the crystals is usually 2,000 ppm or less, preferably 1,000 ppm or less, more preferably 500 ppm or less.
- Ethanol is a low toxic solvent which is classified as Class 3 solvent among residual solvents in pharmaceutical products according to provisions by the Ministry of Health and Welfare. Accordingly, the crystal of the present invention can be preferably used as an active ingredient of pharmaceuticals.
- Crystals were obtained in the same manner as in Example 1 except that the recrystallization solvent was changed to a mixture of ethanol (150 mL) and water (100 mL). The resulting crystals were subjected to differential scanning calorimetry, and as a result, the crystals gave a single endothermic peak approximately at 233° C. Further, the powder X-ray diffraction pattern of these crystals was identical to the powder X-ray diffraction pattern shown in FIG. 6 in Japanese Patent No. 3001632, which verified that the crystals were type-II crystals.
- Crystals were obtained in the same manner as in Example 1 except that the recrystallization solvent was changed to a mixture of ethanol (170 mL) and water (80 mL). The resulting crystals were subjected to differential scanning calorimetry, and as a result, the crystals gave two endothermic peaks approximately at 193° C. and 233° C. These crystals were termed as “type-III crystals”.
- the type-III crystals obtained in Example 3 were heated at 200° C. to 205° C. for 2 hours under reduced pressure.
- the resulting crystals were subjected to differential scanning calorimetry, and as a result, the crystals gave a single endothermic peak approximately at 233° C.
- the powder X-ray diffraction pattern of the resulting crystals was identical to the powder X-ray diffraction pattern shown in FIG. 6 in Japanese Patent No. 3001632, which verified that the crystals were type-II crystals.
- Example 1 and Comparative Example 1 Grain size distributions of the crystals obtained in Example 1 and Comparative Example 1 were measured.
- a laser-type grain size analyzer (Microtrac FRA) was used.
- a 1% aqueous solution of Soprophor FL (3 ml, Rhone-Poulenc) was added with water (15 ml), and an appropriate amount of the crystals obtained in Example 1 or Comparative Example 1 were dispersed in the mixture to obtain a sample dispersion.
- the results are shown in Table 1. As a result, the crystals obtained by the method of the present invention were revealed to have a smaller fluctuation in the average grain size, and found to be suitable for manufacture of tablets with uniform quality.
- the type-II crystals stable against physical impact can be selectively prepared, and the crystals obtained are free from highly toxic hexane as a residual solvent. Accordingly, these crystals can be suitably used as active ingredients of pharmaceutical products. Further, the crystals obtained by the method of the present invention are characterized to have small fluctuation in average grain size, and enable preparation of tablets with a uniform content by a compression process.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000-264733 | 2000-09-01 | ||
| JP2000264733 | 2000-09-01 | ||
| PCT/JP2001/007526 WO2002018322A1 (en) | 2000-09-01 | 2001-08-31 | Process for the production of crystals of a benzoic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20030191342A1 US20030191342A1 (en) | 2003-10-09 |
| US7314639B2 true US7314639B2 (en) | 2008-01-01 |
Family
ID=18752109
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/344,690 Expired - Lifetime US7314639B2 (en) | 2000-09-01 | 2001-08-31 | Process for the production of crystals of a benzoic acid derivative |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7314639B2 (ja) |
| EP (1) | EP1314720B1 (ja) |
| JP (1) | JP4754768B2 (ja) |
| KR (1) | KR100715092B1 (ja) |
| CN (2) | CN1267409C (ja) |
| AT (1) | ATE482926T1 (ja) |
| AU (2) | AU2001284416B2 (ja) |
| CA (1) | CA2420962C (ja) |
| DE (1) | DE60143166D1 (ja) |
| ES (1) | ES2349461T3 (ja) |
| TW (1) | TWI288129B (ja) |
| WO (1) | WO2002018322A1 (ja) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11039995B2 (en) | 2013-03-15 | 2021-06-22 | Samson Pharma, Llc | Topical compositions for reducing the effects of aging |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7084133B2 (en) | 2001-02-09 | 2006-08-01 | Hiroyuki Kagechika | Dicarba-closo-dodecaborane derivatives |
| US20070161105A1 (en) | 2003-03-20 | 2007-07-12 | Reasearch Foundation Itsuu Laboratory | Method of forming organ |
| CN101200435B (zh) * | 2006-12-12 | 2011-12-07 | 江苏恒瑞医药股份有限公司 | 他米巴罗汀ⅱ型结晶的制备方法 |
| KR20100016048A (ko) | 2007-03-30 | 2010-02-12 | 테무릭크 가부시키가이샤 | 타미바로텐 캡슐제 |
| WO2009114966A1 (zh) * | 2008-03-19 | 2009-09-24 | 江苏恒瑞医药股份有限公司 | 他米巴罗汀ii型结晶的制备方法 |
| JP2013216647A (ja) * | 2012-03-14 | 2013-10-24 | Toppan Forms Co Ltd | β−ケトカルボン酸銀の製造方法 |
| US20210002209A1 (en) * | 2018-02-13 | 2021-01-07 | Transgenex Nanobiotech, Inc. | Novel crystalline forms of tamibarotene for treatment of cancer |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4104297A (en) * | 1976-05-12 | 1978-08-01 | Ciba-Geigy Corporation | Thermoplastic polyesters prepared from dicarboxylic acids containing N-heterocyclic rings |
| JPS6122047A (ja) | 1984-07-07 | 1986-01-30 | Koichi Shiyudo | 安息香酸誘導体 |
| EP0170105A2 (en) | 1984-07-07 | 1986-02-05 | Koichi Prof. Dr. Shudo | Benzoic acid derivatives |
| JPS6176440A (ja) | 1984-09-19 | 1986-04-18 | Koichi Shiyudo | 安息香酸誘導体 |
| WO1991014673A1 (fr) | 1990-03-20 | 1991-10-03 | Shionogi & Co., Ltd. | Procede nouveau pour fabriquer un derive d'acide benzoique |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH031632A (ja) * | 1989-05-29 | 1991-01-08 | Nec Corp | 電子メールシステム |
-
2001
- 2001-08-31 US US10/344,690 patent/US7314639B2/en not_active Expired - Lifetime
- 2001-08-31 CN CNB018146538A patent/CN1267409C/zh not_active Expired - Lifetime
- 2001-08-31 ES ES01963406T patent/ES2349461T3/es not_active Expired - Lifetime
- 2001-08-31 AT AT01963406T patent/ATE482926T1/de not_active IP Right Cessation
- 2001-08-31 EP EP01963406A patent/EP1314720B1/en not_active Expired - Lifetime
- 2001-08-31 KR KR1020037002874A patent/KR100715092B1/ko not_active Expired - Lifetime
- 2001-08-31 CA CA002420962A patent/CA2420962C/en not_active Expired - Lifetime
- 2001-08-31 WO PCT/JP2001/007526 patent/WO2002018322A1/ja not_active Ceased
- 2001-08-31 TW TW090121683A patent/TWI288129B/zh not_active IP Right Cessation
- 2001-08-31 DE DE60143166T patent/DE60143166D1/de not_active Expired - Lifetime
- 2001-08-31 AU AU2001284416A patent/AU2001284416B2/en not_active Expired
- 2001-08-31 JP JP2002523440A patent/JP4754768B2/ja not_active Expired - Lifetime
- 2001-08-31 AU AU8441601A patent/AU8441601A/xx active Pending
- 2001-08-31 CN CNA2005101285875A patent/CN1817856A/zh active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4104297A (en) * | 1976-05-12 | 1978-08-01 | Ciba-Geigy Corporation | Thermoplastic polyesters prepared from dicarboxylic acids containing N-heterocyclic rings |
| JPS6122047A (ja) | 1984-07-07 | 1986-01-30 | Koichi Shiyudo | 安息香酸誘導体 |
| EP0170105A2 (en) | 1984-07-07 | 1986-02-05 | Koichi Prof. Dr. Shudo | Benzoic acid derivatives |
| US4703110A (en) | 1984-07-07 | 1987-10-27 | Koichi Shudo | Benzoic acid derivatives having a para substituent which is a substituted phenyl group connected by a linking radical; useful in neoplastic cell differentiation and diagnosis |
| JPS6176440A (ja) | 1984-09-19 | 1986-04-18 | Koichi Shiyudo | 安息香酸誘導体 |
| WO1991014673A1 (fr) | 1990-03-20 | 1991-10-03 | Shionogi & Co., Ltd. | Procede nouveau pour fabriquer un derive d'acide benzoique |
| EP0478787A1 (en) | 1990-03-20 | 1992-04-08 | Shionogi & Co., Ltd. | Novel process for producing benzoic acid derivative |
| US5214202A (en) * | 1990-03-20 | 1993-05-25 | Shionogi & Co., Ltd. | Method for preparing benzoic acid derivatives |
| JP3001632B2 (ja) | 1990-03-20 | 2000-01-24 | 首藤 紘一 | 安息香酸誘導体の新規製造法 |
| JP2000034262A (ja) | 1990-03-20 | 2000-02-02 | Shudo Koichi | 安息香酸誘導体の新規製造法 |
Non-Patent Citations (8)
| Title |
|---|
| Chem. Pharm. Bull., 32, p. 4209-4212, (1984). |
| English Language Abstract of JP 2000-34262. |
| English Language Abstract of JP 61-22047. |
| English Language Abstract of JP 61-76440. |
| English Language Abstract of WO91/14673. |
| J. Cellular Physiology, 135, 179-188 (1988). |
| Kagechika, H. et al., J. Med. Chem. 31, vol. 31 (No. 11), 2182-2192 (1988). |
| Toriumi, Y. et al., J. Org. Chem., vol. 55 (No. 1), 259-263(1990). |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11039995B2 (en) | 2013-03-15 | 2021-06-22 | Samson Pharma, Llc | Topical compositions for reducing the effects of aging |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2420962C (en) | 2009-11-24 |
| CN1267409C (zh) | 2006-08-02 |
| ES2349461T3 (es) | 2011-01-03 |
| CA2420962A1 (en) | 2003-02-28 |
| ATE482926T1 (de) | 2010-10-15 |
| WO2002018322A1 (en) | 2002-03-07 |
| DE60143166D1 (de) | 2010-11-11 |
| EP1314720B1 (en) | 2010-09-29 |
| JP4754768B2 (ja) | 2011-08-24 |
| JPWO2002018322A1 (ja) | 2004-04-08 |
| US20030191342A1 (en) | 2003-10-09 |
| AU8441601A (en) | 2002-03-13 |
| AU2001284416B2 (en) | 2007-02-15 |
| TWI288129B (en) | 2007-10-11 |
| KR20030059117A (ko) | 2003-07-07 |
| EP1314720A4 (en) | 2004-08-18 |
| KR100715092B1 (ko) | 2007-05-07 |
| EP1314720A1 (en) | 2003-05-28 |
| CN1449376A (zh) | 2003-10-15 |
| CN1817856A (zh) | 2006-08-16 |
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